Early-Life, Parental Factors May Help Explain Rising Early-Onset CRC Rates

Demographic, birth, and parental characteristics may influence early-onset colorectal cancer (EOCRC) risk, with male sex, Hispanic ethnicity, high birthweight, and older paternal age emerging as potential risk factors, a new population-based study published in Cancer suggested.¹

Gaps Persist in Understanding What Drives Rising EOCRC Rates

EOCRC, defined as CRC diagnosed before age 50, has become the leading cause of cancer-related death among individuals younger than 50 years in the US. Although overall CRC incidence has declined 45% from its peak between 1985 and 2022, it is rising in adults younger than 65, increasing by 3% per year among patients aged 20 to 49 years and 0.4% per year among those aged 50 to 64 years.² Researchers noted that prior studies have largely focused on adult risk factors, leaving the role of early-life exposures and parental characteristics less understood.¹

To address this gap, investigators conducted a nested case-control study using data from the California Linkage Study of Early-Onset Cancers. The analysis linked California birth records from 1982 through 2021 with statewide cancer registry data collected between 1988 and 2021.

They evaluated a broad range of demographic, birth, maternal, and paternal characteristics. Factors examined included sex, race and ethnicity, birthweight, gestational age, birth order, and delivery mode. Others were maternal age and education, pregnancy complications, maternal birthplace, paternal age, and paternal education. Multivariable logistic regression models were used to estimate associations with EOCRC risk while adjusting for potential confounders.

Demographic, Early-Life Factors May Help Explain Rising EOCRC Rates

The study included 1221 individuals born in California who were diagnosed with EOCRC between the ages of 0 and 39 years and 61,050 cancer-free controls frequency-matched by birth year at a 1:50 ratio. The study population had a mean age at diagnosis of approximately 29 years, and nearly 94% of EOCRC cases occurred among individuals aged 20 to 39 years. Compared with controls, cases were more likely to be male and Hispanic and to have a higher average birthweight.

In adjusted analyses, men had a 34% higher risk of EOCRC compared with women (OR, 1.34; 95% CI, 1.20-1.51), while Hispanic individuals had a 43% higher risk than non-Hispanic White individuals (OR, 1.34; 95% CI, 1.20-1.51). The association between Hispanic ethnicity and EOCRC was particularly evident among individuals aged 20 to 39 years.

The investigators also identified several associations involving parental and birth characteristics. Having a foreign-born mother was associated with a lower risk of EOCRC overall (OR, 0.85; 95% CI, 0.73-0.97), with the protective effect appearing strongest among men. The authors speculated that healthier dietary patterns, lower rates of obesity, and other health-promoting behaviors observed among some immigrant populations may contribute to this finding.

Although higher birthweight was not significantly associated with EOCRC risk in the overall adjusted analysis, among women, every 500-g increase in birthweight corresponded to a 10% increase in EOCRC risk (OR, 1.10; 95% CI, 1.01-1.21). Similarly, women whose fathers were aged 35 years or older at birth had a 56% higher risk of EOCRC than those whose fathers were aged 20 to 24 years (OR, 1.56; 95% CI, 1.08-2.25). Researchers suggested that age-related increases in de novo genetic mutations among older fathers could potentially contribute to this association, although further study is needed.

By contrast, several factors were not significantly associated with EOCRC risk, including gestational age, birth order, mode of delivery, birth plurality, maternal age, maternal education, pregnancy complications, prior miscarriage or stillbirth, maternal history of cesarean delivery, and paternal education.

Results Highlight Need for Further Investigation Into EOCRC Origins

The authors acknowledged several limitations, including the fact that the study could not account for certain potentially important variables, such as maternal obesity, family history of CRC, genetic predisposition, or screening practices. In addition, since it only included individuals diagnosed with EOCRC before age 40, the findings may not be generalizable to those diagnosed between ages 40 and 49 years. Still, the researchers expressed confidence in their findings.

“In this large case-control study nested within the California birth cohort, male sex and Hispanic ethnicity were associated with higher risk of EOCRC, whereas having a foreign-born mother was associated with lower risk of EOCRC among males, in particular,” the authors concluded. “Furthermore, among females, high birthweight and older paternal age were associated with higher risk of EOCRC. These findings require further research for validation and evaluation of possible mechanisms.”

References

1. Siddique S, Wang R, Berardi D, et al. Demographic, birth, parental characteristics, and the risk of early-onset colorectal cancer: a population-based nested case-control study in California. Cancer. 2026;132(13):e70458. doi:10.1002/cncr.70458
2. McCormick B. 2026 ACS report shows CRC rising in younger adults despite overall decline. AJMC^®. March 3, 2026. Accessed June 24, 2026. https://www.ajmc.com/view/2026-acs-report-shows-crc-rising-in-younger-adults-despite-overall-decline